The Limitations of Cytomegalovirus DNA Detection in Cerebrospinal Fluid of Newborn Infants With Congenital CMV Infection: A Tertiary Care Neonatal Center Experience.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection of the central nervous system (CNS) can cause ventriculomegaly, gliosis, calcifications and cortical defects. Detection of CMV DNA in cerebrospinal fluid by PCR (CSF-CMV-PCR) is a marker of CNS involvement. OBJECTIVE: To evaluate a diagnostic value of the positive CSF-CMV-PCR in cCMV. METHODS: Analysis of clinical, laboratory, neuroimaging and single-nucleotide polymorphisms (SNPs) data according to the results of CSF-CMV-PCR were performed in infants with cCMV. RESULTS: A total of 168 infants were included; 145 (86.3%) had negative and 23 (13.7%) had positive CSF-CMV-PCR results. Associations between the positive CSF-CMV-PCR results and prematurity (odds ratio [OR] = 3.24; 95% confidence interval [CI]: 1.30-8.07), microcephaly (OR = 5.67; 95% CI: 2.08-15.41), seizures (OR = 4.15; 95% CI: 1.10-15.67), sensorineural hearing loss (OR = 6.6; 95% CI: 2.49-17.46), splenomegaly (OR = 8.13; 95% CI: 3.12-21.16), hepatitis (OR = 10.51; 95% CI: 3.31-33.35), petechiae (OR = 10.21; 95% CI: 3.78-27.57) and heterozygous T/C genotype at TLR4rs4986791 (OR = 7.88; 95% CI: 1.55-40.12) were observed. When using a multivariate logistic regression analysis, only the presence of severe sensorineural hearing loss (OR = 7.18; 95% CI: 1.75-29.34, P = 0.006), cystic lesions on MRI (OR 5.29; 95% CI: 1.31-21.36, P = 0.02), and calcifications on MRI (OR = 7.19; 95% CI: 1.67-30.97, P = 0.008) remained as the significant independent predictors of the positive CSF-CMV-PCR results. CONCLUSIONS: The detection of CMV DNA in CSF is associated with a higher rate of CNS damage including abnormal MRI neuroimaging and severe hearing loss. Therefore, detection of CMV DNA in CSF may be considered as a marker of severe CNS injury in cCMV infection. However, the very low prevalence of the positive CSF-CMV-PCR results, even in infants with proven CNS involvement, may imply its limited role in clinical practice.

Recommended management of Toxoplasma gondii infection in pregnant women and their children.

Aforesaid recommendations for the management of T.gondii infection, elaborated by the group of experts, are intended for physicians of various specialties in order to standardize and facilitate diagnostic and therapeutic management. Early diagnosis of congenital toxoplasmosis, both symptomatic and asymptomatic, in neonatal period, initiation of adequate treatment and long-term, multispecialist monitoring, including multi-organ rehabilitation of children may prevent or reduce the complications of congenital toxoplasmosis. Health education, whose role is often underestimated, should be targeted mainly on girls and women at reproductive age as to prevent from infection during pregnancy.

Treatment of pediatric epilepsy in Poland.

BACKGROUND: The many types of childhood epilepsies make the diagnosis and treatment difficult and the outcomes frequently poor. Furthermore, there are few clinical trials in pediatric epilepsy that provide useful results to guide daily practice. Therefore for pediatric neurologists expert opinion may be useful. AIMS: To provide an overview of current practice in Poland and compare results with European and US clinical guidelines. METHODS: Polish specialists in pediatric neurology were asked to participate in a survey about pediatric epilepsy. The focus of the questions was on the overall strategy and treatment options for different syndromic diagnoses. The survey was developed and performed according to a previous European survey (Wheless et al., 2007). RESULTS: Fifty-one Polish specialists, working in academic or clinical settings, completed the questionnaire. They limited combination therapy to two or three antiepileptic drugs. Valproate was the treatment of choice for myoclonic, generalized tonic-clonic seizures and Lennox-Gastaut syndrome. For infantile spasms caused by tuberous sclerosis and of symptomatic etiology, vigabatrin was treatment of choice; valproate and ACTH were other first line options. Valproate and ethosuximide were chosen for childhood absence epilepsy and valproate for juvenile absence epilepsy. Carbamazepine was the first-line treatment option for benign partial epilepsy of childhood with centrotemporal spikes and complex partial seizures. In the treatment of juvenile myoclonic epilepsy for males valproate, for females lamotrigine were chosen. CONCLUSION: Polish pediatric neurologists agreed on the majority of questions. Their views reflect the clinical utility and availability of treatment options in Poland. Results may provide direction for clinicians.

Lipoid pneumonia--a case of refractory pneumonia in a child treated with ketogenic diet.

Lipoid pneumonia (LP) is a chronic inflammation of the lung parenchyma with interstitial involvement due to the accumulation of endogenous or exogenous lipids. Exogenous LP (ELP) is associated with the aspiration or inhalation of oil present in food, oil-based medications or radiographic contrast media. The clinical manifestations of LP range from asymptomatic cases to severe pulmonary involvement, with respiratory failure and death, according to the quantity and duration of the aspiration. The diagnosis of exogenous lipoid pneumonia is based on a history of exposure to oil and the presence of lipid-laden macrophages on sputum or bronchoalveolar lavage (BAL) analysis. High-resolution computed tomography (HRCT) is the imaging technique of choice for evaluation of patients with suspected LP. The best therapeutic strategy is to remove the oil as early as possible through bronchoscopy with multiple BALs and interruption in the use of mineral oil. Steroid therapy remains controversial, and should be reserved for severe cases. We describe a case of LP due to oil aspiration in 3-year-old girl with intractable epilepsy on ketogenic diet. Diagnostic problems were due to non-specific symptoms that were mimicking serious infectious pneumonia. A high index of suspicion and precise medical history is required in cases of refractory pneumonia and fever unresponsive to conventional therapy. Gastroesophageal reflux and a risk of aspiration may be regarded as relative contraindications to the ketogenic diet. Conservative treatment, based on the use of oral steroids, proved to be an efficient therapeutic approach in this case.

Long-term effect of everolimus on epilepsy and growth in children under 3 years of age treated for subependymal giant cell astrocytoma associated with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by increased mammalian target of rapamycin (mTOR) activation and growth of benign tumors in several organs throughout the body. In young children with TSC, drug-resistant epilepsy and subependymal giant cell astrocytomas (SEGAs) present the most common causes of mortality and morbidity. There are also some reports on the antiepileptic and antiepileptogenic potential of mTOR inhibitors in TSC. However, the data on everolimus efficacy and safety in young children are very limited. AIMS: To show the long-term safety data and the effect of everolimus treatment on epilepsy in children under the age of 3 who received everolimus for SEGAs associated with TSC. METHODS: We present the results of everolimus treatment in 8 children under the age of 3 who participated in EXIST-1 study. Five patients presented with active, drug-resistant epilepsy at baseline. The mean follow-up is 35 months (33-38 months) and all children are still on treatment. RESULTS: In 6 out of 8 children, at least a 50% reduction in SEGA volume was observed. In 1 child with drug-resistant epilepsy, everolimus treatment resulted in cessation of seizures and in 2 other children, at least a 50% reduction in the number of seizures was noted. The incidence of adverse events (AE) was similar to that observed in older children and adults. CONCLUSIONS: This study suggests that everolimus is effective and safe in infants and young children with epilepsy and SEGA associated with TSC and offers a valuable treatment option.

Antiepileptic treatment before the onset of seizures reduces epilepsy severity and risk of mental retardation in infants with tuberous sclerosis complex.

BACKGROUND: Epilepsy appears in 70-80% of patients with tuberous sclerosis complex, most commonly in the first year of age. Early manifestation of epilepsy is associated with drug-resistant epilepsy and mental retardation in more than 80% of patients. Clinical epileptic seizures are preceded by deterioration of EEG recording thus infants with high risk of epilepsy can be identified. AIMS: We hypothesized that preventative antiepileptic treatment of infants with multifocal activity on EEG might lower the incidence of drug-resistant epilepsy and mental retardation. METHODS: Forty-five infants with early diagnosis of tuberous sclerosis complex were included in the open-label study. They were divided in two groups: standard (n=31) and preventative one (n=14). In standard group the antiepileptic treatment was launched early, but after the onset of seizures. In preventative group medication was commenced when active epileptic discharges were seen on EEG, but before the onset of clinical seizures. Children were followed till the end of 2 years of age. RESULTS: At 24 months of age mental retardation was significantly more frequent and severe in "standard" vs "preventative" group (48% vs 14%; p=0.031; mean IQ score 68.7 vs 92.3; p<0.05). The "preventative" group was characterized by higher ratio of seizure-free patients (93% vs 35%; p=0.004), lower incidence of drug-resistant epilepsy (7% vs 42%; p=0.021) and lower number of patients requiring polytherapy (21% vs 55%; 0.039) than the "standard group. CONCLUSIONS: Preventative antiepileptic treatment of infants with tuberous sclerosis complex and high risk of epilepsy markedly improves their neurodevelopmental outcome and reduces the incidence of drug-resistant seizures.

Cerebral tuber count and its impact on mental outcome of patients with tuberous sclerosis complex.

PURPOSE: The aim of the study was to reveal the relationships between the tuber count of the brain found in patients with tuberous sclerosis complex (TSC) and their cognitive outcome. METHODS: A single-center, retrospective analysis was performed of patients with documented TSC seen from 1988 to 2010 at the Children's Memorial Health Institute, Warsaw, Poland. KEY FINDINGS: Sixty-two patients were analyzed, and there was a significant correlation between younger age at the first seizure and developmental delay. The patients who did not develop seizures had normal development, despite some presenting with higher tuber load than those with seizures. There was a statistically significant negative correlation between the number of tubers within the right temporal lobe and cognition. SIGNIFICANCE: Our findings confirm our hypothesis that the cognitive outcome in TSC is more dependent on the age of the seizure onset rather than on the tuber count.

Successful antiepileptic drug withdrawal in infants with epilepsy and cytomegalovirus neuroinfection: longitudinal study.

PURPOSE: A prospective study estimating antiepileptic and antiviral regimens administered to infants with symptomatic epilepsy and human cytomegalovirus (HCMV) neuroinfection followed for at least 4 years. METHODS: Thirty-two infants (19 female, 13 male) with epileptic seizures and HCMV neuroinfection diagnosed during the first year of life. Detection of HCMV DNA by qualitative polymerase chain reaction (PCR) method in cerebrospinal fluid (CSF), blood leukocytes, and urine confirmed the diagnosis. Infants were treated with intravenous ganciclovir (GCV) and different antiepileptic drugs. All had multiple electroencephalographic and neuroimaging examinations. Outcome of seizures was assessed using Engel classification system in the child's fourth year of life. RESULTS: Cessation of seizures was achieved in 19 infants (59.4%). In 11 children (34.4%) it was possible to withdraw administration of AEDs after 30-36 months. No infantile spasms, generalized tonic-clonic seizures, or polymorphic seizures were observed. They remained seizure-free for 1-6 years without relapse and their psychomotor development was normal. Four patients with intractable epilepsy (class V) had the longest GCV treatment (median 8 weeks). GCV treatment was implemented at the time or within 1 month after the onset of epileptic seizures in 10 of 11 infants withdrawn from AEDs. CONCLUSION: Early introduction of antiepileptic and antiviral GCV regimens in epilepsy and CMV neuroinfection may result in discontinuation of antiepileptic treatment and normal psychomotor development in infants.

Infantile spasms and cytomegalovirus infection: antiviral and antiepileptic treatment.

From 1 January 1995 to 31 December 2004, 22 patients (13 males, nine females; age range 2-12mo) with infantile spasms and cytomegalovirus (CMV) infection were treated with intravenous ganciclovir (GCV) and antiepileptic drugs. GCV was given for 3 to 12 weeks with a 1-month interval (one, two, or three courses). Epileptic spasms occurred before (group A: eight patients), simultaneously (group B: eight patients), and after (group C: six patients) a diagnosis of human CMV (HCMV) infection and antiviral treatment. In 11 patients, DNA CMV [corrected] was found in cerebrospinal fluid by nested-polymerase chain reaction method (neuroinfection). All infants excreted CMV in urine. DNA CMV [corrected] and specific immunoglobulin M and immunoglobulin G antibodies were present in blood. Ten patients, including four with neuroinfection, have been seizure-free for at least the past 18 months. In two patients with neuroinfection, vigabatrin monotherapy was withdrawn after a 2 year 6 month seizure-free period. Eighteen patients required antiepileptic drugs polytherapy, four of whom required additional adrenocorticotropic hormone (ACTH). Six patients on polytherapy were seizure-free on follow-up, two of whom were treated with ACTH, but one patient [corrected] who required ACTH [corrected] was seizure-free on follow-up. In five patients, psychomotor development was normal, 16 had tetraplegia (Gross Motor Function Classification System [GMFCS] Level V), and one had diplegia (GMFCS Level III). Early antiviral and antiepileptic therapy could result in the long-term cessation of seizures.

[Congenital taxoplasmosis in twins in own material]. / Toksoplazmoza u blizniat w materiale wlasnym.

Little is known about congenital toxoplasmosis in twins. As in singletons fetal infection occurs usually in mothers seroconverted during second or third trimester of pregnancy. Infection affects usually both siblings, but there is posible that one child is not infected, especially in dizygotic pregnancies. A distinct difference in clinical patterns between dizygotic and monozygotic twins is observed. In monozygotic pairs most often clinical course is similar, while in dizygotic twins discrepancies in clinical findings are frequent and marked. For almost thirty years of our own experience with congenital toxoplasmosis we observed only four pairs of twins with this intrauterine infection. All of them were dizygotic. In two pairs the clinical course was similar, and different in the other two.

[Longitudinal study of children with bronchopulmonary dysplasia treated with disodium cromoglycate]. / Dlugofalowe obserwacje kliniczne dzieci z dysplazja oskrzelowo-plucna leczonych kromoglikanem dwusodowym.

In order to improve the quality of life of children born prematurely, who developed chronic lung disease, clinical trials of drugs of different origin are undertaken. The aim of the work was the evaluation of the efficacy of disodium cromoglycate in the treatment of bronchopulmonary dysplasia in children. We retrospectively studied 15 infants with bronchopulmonary dysplasia (BPD) hospitalised in the Infant Care Department of Children's Health Memorial Institute from 01.01.1997 to 01.02.2000. All babies were premature (25-30 weeks of gestation) with LBW or VLBW A control group of 11 babies with BPD, matched for birth weight and gestational age, who did not have disodium cromoglycate therapy were also studied. Recurrent obturative bronchitis and bronchial hyperresponsiveness were stated in all cases in both groups. Disodium cromoglycate was administered in all babies in the study group. Inhaled corticosteroid (Budesonide mite) was given in 10 cases, for a short period of time, due to severe obturative bronchitis. Babies in the control group were treated with systemic and inhaled corticosteroids. Results of our trial compared with the log-rank and chi2 test show statistically, significant differences in the regression of obturative bronchitis (log-rank = 4.35, p < 0.0001) and normalization of capillary blood-gas examination (log-rank = 3.777, p < 0.0002) in favour of the studied group, treated with disodium cromoglycate.

[Visual and auditory impairment in children with congenital cytomegalovirus and Toxoplasma gondii infection]. / Zmiany w narzadzie wzroku i sluchu u dzieci z wrodzona toksoplazmoza i cytomegalia.

Intrauterine infections are an important cause of hearing and visual impairment in children. The aim of this paper was to evaluate the character and frequency of hearing and visual disturbances in children with congenital toxoplasmosis and cytomegalovirus infection. 38 out of 54 children with congenital toxoplasmosis as well as 34 out of 403 children with congenital human cytomegalovirus disease, with visual/auditory impairment, hospitalized in Infant Department in Children's Memorial Health Institute between 1995-2001 were enrolled in this study. Visual impairment was observed in all children with toxoplasmosis (with visual dysfunction rate of 74%), but there was no deafness found. Vision impairment had been observed in 18% of children with congenital cytomegalovirus infection compared to 35% of children with auditory impairment (bilateral deafness had been found in half of them). Neurological deficits' rate was much higher in children with toxoplasmosis (52% vs. 4%). Because of common hearing impairment in children with congenital cytomegalovirus infection and vision impairment in children with congenital toxoplasmosis, it is essential to start the prophylaxis to decrease the percentage of handicapped children.